The overall objective of this program project is to improve high dose conformal radiation treatments for cancer by individualizing therapy beyond simple anatomy. The previous grant studied plan optimization, conformal dose distributions, patient related geometrical uncertainties and motion, and dose/volume tolerance boundaries for treatment limiting normal tissues while performing tumor dose escalation without increasing complications. With increasing knowledge of motion and setup uncertainty throughout treatment, and new imaging techniques leading to early predictors of response and toxicity, we now have the opportunity to optimize and individualize each patient's treatment by incorporating events throughout the treatment course. Thus, this program project will work to individualize and optimize the entire planning/delivery process for the patient. tThe first project will develop and evaluate comprehensive adaptive optimization methods, enabling optimization of plans for the entire treatment course incorporating information and events whenever they become available. The second project will study individualization of geometric and dosimetric patient models throughout the treatment course, moving from population-based geometric modeling to individualized models for adaptive treatment delivery. The third project will continue clinical studies of brain and head/neck tumors treated with dose-sculpting techniques, using chemoradiation and improved imaging studying early predictors of response. The fourth project will continue liver and lung studies using dose escalation, chemoradiation, and imaging for predictors of response. The projects are supported by Core - administrative and statistical support, Core - adaptive therapy, Core - quantitative image use, and Core - computer software support. The investigators possess a unique combination of skills and experience which will lead to successful performance of this work, with 18 years experience in clinical 3-D treatment planning, conformal therapy, and clinical studies of dose escalation and normal tissue complications.